{"id":50315,"date":"2023-09-30T10:20:16","date_gmt":"2023-09-30T10:20:16","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=50315"},"modified":"2023-10-07T11:51:36","modified_gmt":"2023-10-07T11:51:36","slug":"nanoparticles-a-booming-drug-delivery-system-in-chemotherapy","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol16no3\/nanoparticles-a-booming-drug-delivery-system-in-chemotherapy\/","title":{"rendered":"Nanoparticles -A Booming Drug Delivery System in Chemotherapy"},"content":{"rendered":"\n

Introduction<\/strong><\/p>\n\n\n\n

Advanced\ndrug delivery methods for targeted sites in chemotherapy are based on\nnanotechnology.  Nanoparticles act as\ndrug carriers for a wide variety of drugs irrespective of their solubility and\npermeability. Researchers are using techniques in the treatment of cancers by\nencapsulating the potent drug in the form of nanoparticles which act as an\nefficient tool in chemotherapy with minimum side effects [1]<\/sup>. Significant\ntoxic and adverse effects of conventional chemotherapy are caused by the toxic\neffect of chemotherapeutic agents on healthy cells. The use of nanotechnology\nin tumour chemotherapy can improve the targeting of anticancer drugs, boost\ntumour killing, and lessen harmful and side effects. One\nof the biggest benefits of nanomaterial-based cancer therapy over free drugs is\ntargeted delivery.<\/p>\n\n\n\n

Chemotherapy\nis the process of treating malignant cells or tumour cells with medicines or\ndrugs. Chemotherapy is given by IV, IM and orally in a systematic order for a\nspecific period. There are various side effects of chemotherapy depending upon\nthe drug dose and its route. To overcome such problems nanoparticles are incorporated\nas a special tool [2]<\/sup>.<\/p>\n\n\n\n

Cancer<\/strong><\/p>\n\n\n\n

Uncontrolled\ncell proliferation and cell division are characteristics of cancer. It might be\nbenign or malignant. Several approaches of novel drug delivery systems are\nbeing utilized to treat cancer [3]<\/sup>. Around the world mortality rate\nis very high due to late detection and insufficient treatment for cancer. A\nwide variety of treatments are available including radiation, surgery, immune\ntherapy, targeted therapy, hormone therapy etc. depending upon the stage and\ntolerance and response of patients. The development of anti-cancer agents is a\ncomplex procedure because of the selection of suitable chemical moiety for drug\nentrapment [4]<\/sup>. Nanoparticles can increase the intracellular amount\nof medications in cancer cells while reducing their toxic effect in normal\ncells by employing both passive and active targeting tactics. Because of the\nimproved permeability and retention (EPR) capabilities of nanocarriers, passive\ntargeting takes use of the biological characteristics of tumours. [5]<\/sup>\nActive strategies accomplish this by coupling molecules that attach to promote the target cells’\noverexpression of antigens or receptors to nanocarriers that contain\nchemotherapeutics.<\/p>\n\n\n\n

Nanoparticles<\/strong><\/p>\n\n\n\n

Drug\nhalf-life can be extended by nano-carriers, which can also lead to their\naccumulation in tumour tissues because of the size, surface, and\nretention-enhancing properties of NPs. [6] <\/sup>The choice of a targeted\ndrug delivery system is a need in cancer treatment. Thus, nanotechnology act as\na boon in the field of nanomedicine. The major challenge is to discriminate the\nmalignant cells from the healthy cells of the body. Current chemotherapy has\nissues with cytotoxicity, lack of selectivity, low solubility, short half-lives,\nthe incidence of multi-drug resistance, and the development of stem-like cells.\nNanomaterial-based chemotherapy, molecular therapy targeted therapy,\nphotodynamic therapy, sono-dynamic therapy, and photothermal therapy are all used\nto treat cancer to get around these limitations. Nanoparticles are the new drug\ndelivery system utilized in targeted therapy [7]<\/sup>. They are having a size\nrange of less than 100 nm and can encapsulate a wide variety of drugs which enhances\ntheir solubility and permeability. Solubility is a major problem in\nchemotherapeutic agents. Nanoparticles can administer chemotherapeutic\ntreatments with various benefits compared to using free medications directly.\nSome of them have to do with the fact that chemotherapeutic drugs can become\nmore stable and solubilize better when delivered by nanoparticles, while\nintravenous administration of nanoparticle-delivered drugs can enhance\nbiodistribution, prolong circulation time, and lessen the side effects of\nchemotherapy reactions. A\nwide range of prodrugs can be encapsulated in nanoparticles for target drug\ndelivery. These drugs are target specific and only show their response after\nactivation at the actual diseased cell in case of a tumour [8]<\/sup>. Example:\ncisplatin. The\nbrain-blood barrier (BBB) is a unique defence mechanism designed to shield the\ncentral nervous system (CNS) from poisonous and damaging substances. The “brain\ncapillary endothelial cells” are organized to form a wall that feeds the\nbrain with vital nutrients. Since the BBB’s main purpose is to prevent\nhazardous substances from entering the brain, the only effective\nchemotherapeutic treatments for brain cancer at the moment are intracerebral\ninfusions or intraventricular. [8]<\/sup> But NPs have been known to cross\nthe BBB. Currently, Nanoparticles are delivered by a variety of methods,\nincluding transcytosis, the EPR effect, targeted ultrasound, and\npeptide-modified endocytosis. Methotrexate absorption in rats was improved by\nglutathione PEGylated liposomes that were encapsulated with the drug. [9]<\/sup>\nDue to their ability to carry medications that cause apoptosis, AuNPs are\nfrequently employed.<\/p>\n\n\n\n

Mechanism of Tumor\ntargeting<\/strong><\/p>\n\n\n\n

Active Targeting<\/strong><\/p>\n\n\n\n

Through\nactive interaction between receptors and ligands, active targeting precisely\ntargets cancer cells. Targeted cells are distinguished from normal cells by the\nligands on the surface of NPs, which are selected to focus on the target molecules\nthat are abundantly expressed on the cancer cell’s surface. When ligands on\nNanoparticles interact with receptors on the surface of cancer cells, a process\nknown as receptor-mediated endocytosis occurs, successfully releasing\ntherapeutic drugs from internalized Nanoparticles. [11] Active targeting is\nideally suited for the delivery of macromolecular medicines like proteins and\nsiRNAs due to their nature. Monoclonal antibodies, amino acids, peptides, carbohydrates\nand vitamins are examples of targeting moieties. [12] <\/sup>The folate\nreceptor, transferrin receptor, epidermal growth factor receptor, and\nglycoproteins, are among the receptors that are extensively investigated. These\nligands precisely attach to cell-specific receptors (EGFR).Examples:\nEGFR, a tyrosine kinase (TK) receptor from the ErbB family, is overexpressed in\nseveral cancer forms, particularly those with squamous cell histology. Human\nSCC can be targeted using gold nanoparticles using anti-IgG-PEG-AuNPs and\nanti-EGFR-PEG-AuNPs. Human EGF receptor-2 (HER2), which is overexpressed on the\nsurfaces of breast cancer cells, is inhibited by the drug Herceptin\u00ae.\nHER2-targeted PEGylated liposomal doxorubicin was developed to decrease\ncardiotoxicity, a common side effect of anthracyclines.<\/p>\n\n\n\n

Passive Targeting<\/strong><\/p>\n\n\n\n

Passive\ntargeting’s goal is to focus on the variations between tumours and healthy\ntissue. By using passive targeting, drugs are successfully delivered to the\ntarget spot where they can carry out a therapeutic action. Neovascularization\nis a result of high cancer cell proliferation, and large holes in the vascular\nwall increase the perm selectivity of tumour arteries in comparison to healthy\nvessels. [13] Due to the rapid and inadequate angiogenesis, macromolecules,\nsuch as Nanoparticles, may leak from blood vessels supporting the tumour and\nconcentrate within tumour tissue. Due to insufficient lymphatic drainage, which\nallows the nano-carriers to transport their contents to tumour cells, the\nretention of Nanoparticles is enhanced in cancer. The EPR effect, one of the\nforces underlying passive targeting, is produced by these processes. [14]<\/sup> Numerous studies have demonstrated that\nthe size of Nanoparticles has an impact on the EPR effect because smaller Nanoparticles\nhave higher penetrability but do not leak into healthy vasculature. [15]<\/sup>\nHowever, larger particles have a higher chance of being eliminated by the\nimmune system. Example: Abraxane\u00ae (albumin-bound paclitaxel, Abraxis\nBio-Sciences), used to treat advanced or metastatic breast cancer, was given US\nFDA approval in 2005. (MBC). A cancer treatment called DaunoXome\u00ae (liposomal\ndaunorubicin; Gilead Science\/Diatos) slows the proliferation of malignant\ncells. Daunorubicin is an active chemical. The treatment for Kaposi’s sarcoma,\na type of cancer that affects the lungs, intestines, and skin, uses a special\nformulation of daunorubicin (in liposome form). In 1996, US FDA gave its\napproval. [16]<\/sup><\/p>\n\n\n\n

Retention\neffect and enhanced permeability <\/strong><\/p>\n\n\n\n

The\nvasculatures of tumours are typically abnormal, with misaligned branching and\nporous walls [17]. The rapid proliferation of endothelial cells and the\ndecreased number of pericytes are the causes of this leakiness. Due to these\nfeatures, tumour vasculatures have large pores with diameters between 100 nm\nand several hundred nm as opposed to the 5\u201310 nm of normal vessel junctions.\nBecause of the larger pores, tumours have higher levels of vascular\npermeability and hydraulic conductivity, which makes it possible for\nmacromolecules like nanoparticles to enter tumours [18]. The lymphatic system\nremoves macromolecules from healthy tissue. However, weakened lymphatics are\ntypically present in solid tumours [19]. Lymphatic vessels are compressed by\nexpanding tumour cells, which also cause the majority of the vessels to\ncollapse, particularly in the tumour\u2019s centre. The EPR effect is caused by the\ncompromised lymphatic system and enhanced permeability of the tumour\nvasculature. Similar to other macromolecules, nanoparticles have longer\nretention durations in tumours, causing their concentrations to be higher than in\nplasma or other tissues. As a result, nanoparticles can passively target\ntumours via the EPR effect.<\/p>\n\n\n\n

Nanoparticle Targeted\nDelivery<\/strong><\/p>\n\n\n\n

Anticancer\ndrugs should ideally be able to pass through physiological barriers after\nadministration and reach the targeted tumour tissues with low volume loss or\nblood circulation activity to be successful in the treatment of cancer. Second,\nonce the drugs have reached the desired location, they ought to be very\nselective in their ability to kill cancer cells while sparing healthy cells.\nThese two primary strategies are also linked to improvements in patient\nlongevity and quality of life by increasing the intracellular concentration of\ndrugs while reducing toxicities related to dose-limiting dosages. A growing\nbody of research indicates that nanoparticles might be able to satisfy both of\nthese requirements for effective medication delivery systems. [20]<\/sup><\/p>\n\n\n\n

Advantages[21]<\/sup><\/strong><\/p>\n\n\n\n

Enhance the stability of drugs.<\/p>\n\n\n\n

Increases encapsulation efficiency.<\/p>\n\n\n\n

Reduces dose frequency.<\/p>\n\n\n\n

They have higher carrier capacity.<\/p>\n\n\n\n

It can also be utilized as controlled drug delivery.<\/p>\n\n\n\n

It possesses active as well as passive targeting of tumour cells.<\/p>\n\n\n\n

It enhanced solubility and bioavailability due to the presence of organic moieties.<\/p>\n\n\n\n

Modification of the surface can be easily done.<\/p>\n\n\n\n

It enhanced therapeutic activity.<\/p>\n\n\n\n

Site-specific targeting.<\/p>\n\n\n\n

Reduce toxicity.<\/p>\n\n\n\n

Oral, nasal, and parenteral routes can be used for administration.<\/p>\n\n\n\n

Hydrophilic, and hydrophobic drugs can be used.<\/p>\n\n\n\n

Types of Nanoparticles [21,22]<\/sup><\/strong><\/p>\n\n\n\n

Wide varieties of polymers are utilized in the preparation of nanoparticles like PEG, and Chitosan, for delivering anti-cancer agents. <\/p>\n\n\n\n

Polymeric nanoparticles: e.g.: Nanocapsules, Nanospheres, micelles, Nano gels, dendrimers.<\/p>\n\n\n\n

Lipid-based nanoparticles: e.g.: SLN, phospholipid micelles, liposomes.<\/p>\n\n\n\n

Inorganic nanoparticles: e.g.: gold nanoparticles, silver nanoparticles, mesoporous silica nanoparticles.<\/p>\n\n\n\n

Polymers used<\/strong><\/p>\n\n\n\n

Natural polymers: proteins, gelatin, albumin, dextran, chitosan<\/p>\n\n\n\n

Synthetic polymers: polystyrene, polyacrylate.<\/p>\n\n\n\n

Semi-synthetic polymers: cellulose derivatives<\/p>\n\n\n\n

Techniques of preparation of nanoparticles [23]<\/sup><\/strong><\/p>\n\n\n\n

Different physical and chemical, biochemical, and biological methods are utilized for producing nanoparticles. Approaches like emulsification, precipitation, spray drying, salting out and nano-emulsification are used in preparation.<\/p>\n\n\n\n

Emulsion-Solvent evaporation Method<\/strong><\/p>\n\n\n\n

It is a common method of preparation of nanoparticles involving two steps, in the first step polymer emulsification solution in the aqueous phase is followed by evaporation of the polymer to form Nanospheres by precipitation reaction. Ultracentrifugation is done for the collection of drug-loaded nanoparticles.<\/p>\n\n\n\n

Double Emulsion & Evaporation Method<\/strong><\/p>\n\n\n\n

This technique is used for hydrophilic drugs because of poor entrapment efficiency. W\/o emulsion is prepared and to this emulsion, another aqueous phase is added with continuous stirring to obtain a w\/o\/w type of emulsion. In the next step, the solvent is evaporated and nanoparticles are obtained by centrifugation.<\/p>\n\n\n\n

Salting-out Method<\/strong><\/p>\n\n\n\n

It is a modified emulsification\/solvent diffusion method in which the drug and polymer are dissolved in a suitable vehicle and added to an aqueous gel consisting of electrolyte agents (salting-out agent) with colloidal stabilizers.<\/p>\n\n\n\n

Polymerization Method<\/strong><\/p>\n\n\n\n

In this method, a polymerization\nreaction is induced in monomers in an aqueous environment as soon as\npolymerization is completed drug is entrapped onto the nanoparticles by the adsorption\nmethod.<\/p>\n\n\n\n

Evaluation Parameters [24]<\/sup><\/strong><\/p>\n\n\n\n

Particle size: the particle size of the nanoparticle is determined by SEM scanning electron microscopy and TEM transition electron microscopy.<\/p>\n\n\n\n

In vitro drug release study: It is done by using a USP Type II dissolution apparatus with 900 ml phosphate buffer at 37\u00b10.20<\/sup>C temperature at a rotation speed of 50 rpm.<\/p>\n\n\n\n

Stability of nanoparticle: prepared nanoparticles preparation is placed in a stability chamber for 90 days at a temperature range of 40<\/sup> C \u00b110 <\/sup>C and 300<\/sup> C \u00b1 20<\/sup> C.<\/p>\n\n\n\n

Structure and crystallinity: TheX-ray diffraction method is used to identify the structure and crystallinity of the formulation.<\/p>\n\n\n\n

Yield of nanoparticles: % Yield = Amount of nanoparticle \/ Amount of drug + polymer x 100<\/p>\n\n\n\n

Surface charge: The surface charge of the nanoparticle is identified by Zeta-potential analysis.<\/p>\n\n\n\n

Drug content: the drug content is identified by UV spectrophotometer analysis or by HPLC technique.<\/p>\n\n\n\n

Application<\/strong><\/p>\n\n\n\n

In cancer therapy<\/p>\n\n\n\n

Intracellular targeting<\/p>\n\n\n\n

As a vaccine adjuvant<\/p>\n\n\n\n

For DNA delivery<\/p>\n\n\n\n

Ocular delivery<\/p>\n\n\n\n

For skin and hair care therapy<\/p>\n\n\n\n

It can also be effective to cross the blood-brain barrier<\/p>\n\n\n\n

It can also be used for diagnostic purposes<\/p>\n\n\n\n

Conclusion<\/strong><\/p>\n\n\n\n

A new era in cancer\ntreatment has been brought in by the use of nanotechnology in cancer therapy. In comparison to conventional drugs,\nNanoparticle drug delivery methods have better tumour targeting,\npharmacokinetics, stability and biocompatibility. They also contribute\nsignificantly to lowering systemic toxicity and combating drug resistance. Due\nto these benefits, Nanoparticle medications are frequently used in targeted\ntherapy, gene therapy, hyperthermia, chemotherapy and radiation. Nanoparticles\nare an efficient weapon in the treatment of cancer because of their improved,\nenhanced, efficient target drug delivery, and better bioavailability with\nminimum side effects. To enhance their biodistribution and lengthen their stay\nin the bloodstream, nanoparticles have been engineered for the best surface and\nsize properties. Utilizing the EPR effect, passive targeting can enhance the\nexposure period of tumour cells to cytotoxic drugs, lengthen the duration that\ndrugs remain in the body’s bloodstream, and decrease the number of harmful side\neffects. To develop selective nanoparticle drug delivery systems that recognize\ncertain targets, active targeting makes use of several compounds that are\noverexpressed in tumour cells. Chemotherapeutic agents like Doxil and Abraxane\nare the milestones in chemotherapy which shows improved efficacy as compared to\nconventional dosage forms. Drugs can be encapsulated in vast quantities without\nundergoing any chemical reactions. In comparison to analogous passive targeted\ndrug delivery systems, active targeted drug delivery systems are anticipated to\noffer enormous advantages. There is no question that in the future,\nnanocarriers, particularly NP-based drug delivery systems, will be the primary\nform of treatment.<\/p>\n\n\n\n

Acknowledgment<\/strong><\/p>\n\n\n\n

Authors conveyed special thanks to Mr.\nJitender Joshi, Chancellor, and Prof. (Dr.) Dharam Buddhi, Vice Chancellor of\nUttaranchal University encourages us for writing this communication.<\/strong><\/p>\n\n\n\n

Conflict of interest <\/strong>
\n<\/strong>The authors declare that there is no conflict of\ninterest.<\/p>\n\n\n\n

Funding<\/strong> Sources<\/strong><\/p>\n\n\n\n

The authors declare that no funds, grants,\nor other support were received during the preparation of this manuscript.<\/p>\n\n\n\n

References<\/strong><\/p>\n\n\n\n

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